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Maternal Western-style high fat diet induces sex-specific physiological and molecular changes in two-week-old mouse offspring.

Mischke M, Pruis MG, Boekschoten MV, Groen AK, Fitri AR, van de Heijning BJ, Verkade HJ, Müller M, Plösch T, Steegenga WT - PLoS ONE (2013)

Bottom Line: Exclusively male offspring had significantly higher body weight upon maternal WSD.Only 10% of these significantly changed genes overlapped in both sexes.We conclude that maternal WSD affects physiological parameters and induces substantial changes in the molecular profile of the liver in two-week-old pups.

View Article: PubMed Central - PubMed

Affiliation: Nutrition, Metabolism & Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.

ABSTRACT
Maternal diet is associated with the development of metabolism-related and other non-communicable diseases in offspring. Underlying mechanisms, functional profiles, and molecular markers are only starting to be revealed. Here, we explored the physiological and molecular impact of maternal Western-style diet on the liver of male and female offspring. C57BL/6 dams were exposed to either a low fat/low cholesterol diet (LFD) or a Western-style high fat/high cholesterol diet (WSD) for six weeks before mating, as well as during gestation and lactation. Dams and offspring were sacrificed at postnatal day 14, and body, liver, and blood parameters were assessed. The impact of maternal WSD on the pups' liver gene expression was characterised by whole-transcriptome microarray analysis. Exclusively male offspring had significantly higher body weight upon maternal WSD. In offspring of both sexes of WSD dams, liver and blood parameters, as well as hepatic gene expression profiles were changed. In total, 686 and 604 genes were differentially expressed in liver (p≤0.01) of males and females, respectively. Only 10% of these significantly changed genes overlapped in both sexes. In males, in particular alterations of gene expression with respect to developmental functions and processes were observed, such as Wnt/beta-catenin signalling. In females, mainly genes important for lipid metabolism, including cholesterol synthesis, were changed. We conclude that maternal WSD affects physiological parameters and induces substantial changes in the molecular profile of the liver in two-week-old pups. Remarkably, the observed biological responses of the offspring reveal pronounced sex-specificity.

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Heat map of Wnt/beta-catenin pathway.The Wnt/beta-catenin gene set was hierarchically clustered based on Pearson correlation. Gene expression values are displayed on colour scale: blue indicates lower values than average of maternal LFD-group of respective sex; orange indicates higher values than average of maternal LFD-group of respective sex. (m) = gene was significantly changed in male offspring upon maternal WSD. (f) = gene was significantly changed in female offspring upon maternal WSD. p-values≤0.01 were considered significant.
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pone-0078623-g004: Heat map of Wnt/beta-catenin pathway.The Wnt/beta-catenin gene set was hierarchically clustered based on Pearson correlation. Gene expression values are displayed on colour scale: blue indicates lower values than average of maternal LFD-group of respective sex; orange indicates higher values than average of maternal LFD-group of respective sex. (m) = gene was significantly changed in male offspring upon maternal WSD. (f) = gene was significantly changed in female offspring upon maternal WSD. p-values≤0.01 were considered significant.

Mentions: Various pathways and sub-functions correspond to biological function categories in IPA. Figure 4 and 5 display heat maps of gene sets that relate either to developmental or metabolic functions, which were regulated upon maternal WSD according to IPA. Represented gene sets were received from the integrated knowledge base of IPA and the KEGG pathway database. Only genes significantly differing in gene expression depending on maternal diet in at least one of the sexes are displayed.


Maternal Western-style high fat diet induces sex-specific physiological and molecular changes in two-week-old mouse offspring.

Mischke M, Pruis MG, Boekschoten MV, Groen AK, Fitri AR, van de Heijning BJ, Verkade HJ, Müller M, Plösch T, Steegenga WT - PLoS ONE (2013)

Heat map of Wnt/beta-catenin pathway.The Wnt/beta-catenin gene set was hierarchically clustered based on Pearson correlation. Gene expression values are displayed on colour scale: blue indicates lower values than average of maternal LFD-group of respective sex; orange indicates higher values than average of maternal LFD-group of respective sex. (m) = gene was significantly changed in male offspring upon maternal WSD. (f) = gene was significantly changed in female offspring upon maternal WSD. p-values≤0.01 were considered significant.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3818485&req=5

pone-0078623-g004: Heat map of Wnt/beta-catenin pathway.The Wnt/beta-catenin gene set was hierarchically clustered based on Pearson correlation. Gene expression values are displayed on colour scale: blue indicates lower values than average of maternal LFD-group of respective sex; orange indicates higher values than average of maternal LFD-group of respective sex. (m) = gene was significantly changed in male offspring upon maternal WSD. (f) = gene was significantly changed in female offspring upon maternal WSD. p-values≤0.01 were considered significant.
Mentions: Various pathways and sub-functions correspond to biological function categories in IPA. Figure 4 and 5 display heat maps of gene sets that relate either to developmental or metabolic functions, which were regulated upon maternal WSD according to IPA. Represented gene sets were received from the integrated knowledge base of IPA and the KEGG pathway database. Only genes significantly differing in gene expression depending on maternal diet in at least one of the sexes are displayed.

Bottom Line: Exclusively male offspring had significantly higher body weight upon maternal WSD.Only 10% of these significantly changed genes overlapped in both sexes.We conclude that maternal WSD affects physiological parameters and induces substantial changes in the molecular profile of the liver in two-week-old pups.

View Article: PubMed Central - PubMed

Affiliation: Nutrition, Metabolism & Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.

ABSTRACT
Maternal diet is associated with the development of metabolism-related and other non-communicable diseases in offspring. Underlying mechanisms, functional profiles, and molecular markers are only starting to be revealed. Here, we explored the physiological and molecular impact of maternal Western-style diet on the liver of male and female offspring. C57BL/6 dams were exposed to either a low fat/low cholesterol diet (LFD) or a Western-style high fat/high cholesterol diet (WSD) for six weeks before mating, as well as during gestation and lactation. Dams and offspring were sacrificed at postnatal day 14, and body, liver, and blood parameters were assessed. The impact of maternal WSD on the pups' liver gene expression was characterised by whole-transcriptome microarray analysis. Exclusively male offspring had significantly higher body weight upon maternal WSD. In offspring of both sexes of WSD dams, liver and blood parameters, as well as hepatic gene expression profiles were changed. In total, 686 and 604 genes were differentially expressed in liver (p≤0.01) of males and females, respectively. Only 10% of these significantly changed genes overlapped in both sexes. In males, in particular alterations of gene expression with respect to developmental functions and processes were observed, such as Wnt/beta-catenin signalling. In females, mainly genes important for lipid metabolism, including cholesterol synthesis, were changed. We conclude that maternal WSD affects physiological parameters and induces substantial changes in the molecular profile of the liver in two-week-old pups. Remarkably, the observed biological responses of the offspring reveal pronounced sex-specificity.

Show MeSH
Related in: MedlinePlus